HDAC3 was found to associate with TYK2 and contributed to activation of the TYK2-STAT1-BCL2 signaling pathway in T-ALL cells.<h4>Conclusion</h4>Our results highlight the effectiveness of the combination of chidamide and chemotherapy in the treatment of T-ALL patients and suggest that HDAC3 can act as a potential novel therapeutic target to inhibit the TYK2-STAT1-BCL2 signaling pathway in T-ALL. Here, TYK2 is linked to acute lymphoblastic leukemia.